This is an application for continued support for years 36-40 of a postdoctoral training program in genetics based in the Department of Molecular and Human Genetics (DMHG). The DMHG is a bridging department with major clinical activities and strong programs in basic science research, but the emphasis of this postdoctoral program is on medical and human genetics and on molecular approaches. There are 79 training faculty, 58 with primary and 21 with secondary appointments in the DMHG. Dr. Beaudet, the current Chair of the DMHG, has served as Program Director for many years and as part of a planned leadership transition of this program, Dr. Lee will be the Program Director starting in 2012. Major research areas in the Program include identifying human disease genes, molecular diagnostics including whole exome analysis, molecular cytogenetics including array CGH, biochemical studies of inborn errors of metabolism, genomic imprinting, molecular dysmorphology, cell and gene therapy, developmental biology and gene targeting in the mouse, genetic control of morphogenesis and development in Drosophila, control of cell cycle, genomic instability, bacterial recombination, genomic sequencing, and genetics of neurological disorders. Trainees include MD or MD/PhD candidates seeking combined clinical and research training or seeking strictly research training, trainees of various degrees seeking combined laboratory diagnostic and research training, and PhD trainees seeking primarily research training in human or nonhuman genetics. The MD trainees generally have completed primary training in pediatrics, medicine, or clinical genetics and PhD trainees most often come directly from completion of graduate school. A major focus of the program is to attract highly qualified MD and MD/PhD trainees who seek clinical training but are also seeking an intensive and substantial research experience. Major strengths of the training environment include a large clinical genetics component; large and sophisticated diagnostic laboratories in cytogenetics, biochemical genetics, and molecular genetics; 130,000 square feet of space for the department's various research, clinical, and administrative activities; strong institutional commitment; a genetic graduate student program with relevant course work; an American Board of Medical Genetics (ABMG) certified training program; a high national ranking for research funding; a large program in human genomic sequencing; an NIH funded Intellectual and Developmental Disability Research Center; an NIH funded Mendelian Disease Sequencing Center, and overall depth in molecular genetics.